Consistent Alterations of Circulating Matrix Metalloproteinases Levels in Untreated Hypertensives and in Spontaneously Hypertensive Rats: A Relevant Pharmacological Target

Inconsistent matrix metalloproteinases (MMPs) levels have been reported in hypertension, with higher, similar and lower MMPs levels reported in hypertensives compared with normotensives. Differences between studies may reflect lack of control of drug effects, accompanying diseases and pre-analytical issues. We compared MMP-2, MMP-8 and MMP-9 levels in 38 untreated hypertensive patients (with no other diseases) with those found in 33 normotensive controls. We also studied endogenous MMPs inhibitors (TIMP-1, TIMP-2 and alpha-2-macroglobulin-A2M). Additionally, we assessed MMPs and A2M levels in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. We hypothesized that similar MMPs/endogenous inhibitors` profiles would be found in this animal model of hypertension and in clinical hypertension. MMPs, TIMPs and A2M were measured in plasma samples with commercially available ELISA and gelatin zymography. We found unaltered MMP-2, MMP-8, TIMP-1, TIMP-2 and A2M levels in hypertension. However, hypertensives had higher MMP-9 levels and MMP-9/A2M ratios than normotensives. Moreover, while we found similar MMP-2 and A2M levels in SHR and WKY rats, we found higher MMP-9 levels and MMP-9/A2M ratios in SHR versus WKY rats. These findings show consistent abnormal net plasma MMP-9 (but not MMP-2) activity in clinical and experimental hypertension. These parallel alterations in clinical hypertension and in SHR suggest an important role for MMPs in hypertension. While MMPs may be a relevant pharmacological target, antihypertensive drugs that down-regulate MMPs may offer advantages in the management of this disease.

Efficacy of Marigold Extract-Loaded Formulations Against UV-induced Oxidative Stress

The present study investigated the potential use of topical formulations containing marigold extract (ME) (Calendula officinalis extract) against ultraviolet (UV) B irradiation-induced skin damage. The physical and functional stabilities, as well as the skin penetration capacity, of the different topical formulations developed were evaluated. In addition, the in vivo capacity to prevent/treat the UVB irradiation-induced skin damage, in hairless mice, of the formulation with better skin penetration capacity was investigated. All of the formulations were physically and functionally stable. The gel formulation [Formulation 3 (F3)] was the most effective for the topical delivery of ME, which was detected as 0.21 mu g/cm(2) of narcissin and as 0.07 mu g/cm(2) of the rutin in the viable epidermis. This formulation was able to maintain glutathione reduced levels close to those of nonirradiated animals, but did not affect the gelatinase-9 and myeloperoxidase activities increased by exposure to UVB irradiation. In addition, F3 reduced the histological skin changes induced by UVB irradiation that appear as modifications of collagen fibrils. Therefore, the photoprotective effect in hairless mice achieved with the topical application of ME in gel formulation is most likely associated with a possible improvement in the collagen synthesis in the subepidermal connective tissue. (C) 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:2182-2193, 2011

Accuracy and cost- and time-effectiveness of digital clip versus videotape interpretation of echocardiograms in patients with valvular disease

Background. Although digital and videotaped images are known to be comparable for the evaluation of left ventricular function, their relative accuracy for assessment of more complex anatomy is unclear. We sought to compare reading time, storage costs, and concordance of video and digital interpretations across multiple observers and sites. Methods. One hundred one patients with valvular (90 mitral, 48 aortic, 80 tricuspid) disease were selected prospectively, and studies were stored according to video and standardized digital protocols. The same reviewer interpreted video and digital images independently and at different times with the use of a standard report form to evaluate 40 items (eg, severity of stenosis or regurgitation, leaflet thickening, and calcification) as normal or mildly, moderately, or severely abnormal Concordance between modalities was expressed at kappa Major discordance (difference of >1 level of severity) was ascribed to the modality that gave the lesser severity. CD-ROM was used to store digital data (20:1 lossy compression), and super-VHS video-tape was used to store video data The reading time and storage costs for each modality were compared Results. Measured parameters were highly concordant (ejection fraction was 52% +/- 13% by both). Major discordance was rare, and lesser values were reported with digital rather than video interpretation in the categories of aortic and mitral valve thicken ing (1% to 2%) and severity of mitral regurgitation (2%). Digital reading time was 6.8 +/- 2.4 minutes, 38% shorter than with video (11.0 +/- 3.0, range 8 to 22 minutes, P < .001). Compressed digital studies had an average size of 60 <plus/minus> 14 megabytes (range 26 to 96 megabytes). Storage cost for video was A$0.62 per patient (18 studies per tape, total cost A$11.20), compared with A$0.31 per patient for digital storage (8 studies per CD-ROM, total cost A$2.50). Conclusion. Digital and video interpretation were highly concordant; in the few cases of major discordance, the digital scores were lower, perhaps reflecting undersampling. Use of additional views and longer clips may be indicated to minimize discordance with video in patients with complex problems. Digital interpretation offers a significant reduction in reading times and the cost of archiving.

Prediction of mortality using dobutamine echocardiography

OBJECTIVES We sought to find out whether dobutamine echocardiography (DbE) could provide independent prediction of total and cardiac mortality, incremental to clinical and angiographic variables. BACKGROUND Existing outcome studies with DbE have examined composite end points, rather than death, over a relatively short follow-up. METHODS Clinical and stress data were collected in 3,156 patients (age 63 +/- 12 years, 1,801 men) undergoing DbE. Significant stenoses (>50% diameter) were identified in 70% of 1,073 patients undergoing coronary angiography. Total and cardiac mortality were identified over nine years of follow-up (mean 3.8 +/- 1.9). Cox models were used to analyze the effect of ischemia and other variables, independent of other determinants of mortality. RESULTS The dobutamine echocardiogram was abnormal in 1,575 patients (50%). Death occurred in 716 patients (23%), 259 of whom (8%) were thought to have died from cardiac causes. Patients with normal DbE had a total mortality of 8% per year and a cardiac mortality of 1% per year over the first four years of follow-up. Ischemia and the extent of abnormal wall motion were independent predictors of cardiac death, together with age and heart failure. In sequential Cox models, the predictive power of clinical data alone (model chi-square 115) was strengthened by adding the resting left ventricular function (model chi-square 138) and the results of DbE (model chi-square 181). In the subgroup undergoing coronary angiography, the power of the model was increased to a minor degree by the addition of coronary anatomy data. CONCLUSIONS Dobutamine echocardiography is an independent predictor of death, incremental to other data. While a normal dobutamine echocardiogram predicts low risk of cardiac death ton the order of 1% per year), this risk increases with the extent of abnormal wall motion at rest and stress, (J Am Coil Cardiol 2001;37:754-60) (C) 2001 by the American College of Cardiology.

Development of a fully quantitative approach to the interpretation of stress echocardiography using radial and longitudinal myocardial velocities

Background: Tissue Doppler may be used to quantify regional left ventricular function but is limited by segmental variation of longitudinal velocity from base to apex and free to septal walls. We sought to overcome this by developing a composite of longitudinal and radial velocities. Methods and Results. We examined 82 unselected patients undergoing a standard dobutamine echocardiogram. Longitudinal velocity was obtained in the basal and mid segments of each wall using tissue Doppler in the apical views. Radial velocities were derived in the same segments using an automated border detection system and centerline method with regional chords grouped according to segment location and temporally averaged. In 25 patients at low probability of coronary disease, the pattern of regional variation in longitudinal velocity (higher in the septum) was the opposite of radial velocity (higher in the free wall) and the combination was homogenous. In 57 patients undergoing angiography, velocity in abnormal segments was less than normal segments using longitudinal (6.0 +/- 3.6 vs 9.0 +/- 2.2 cm/s, P = .01) and radial velocity (6.0 +/- 4.0 vs 8.0 +/- 3.9 cm/s, P = .02). However, the composite velocity permitted better separation of abnormal and normal segments (13.3 +/- 5.6 vs 17.5 +/- 4.2 cm/s, P = .001). There was no significant difference between the accuracy of this quantitative approach and expert visual wall motion analysis (81% vs 84%, P = .56). Conclusion: Regional variation of uni-dimensional myocardial velocities necessitates site-specific normal ranges, probably because of different fiber directions. Combined analysis of longitudinal and radial velocities allows the derivation of a composite velocity, which is homogenous in all segments and may allow better separation of normal and abnormal myocardium.

Quality of care of patients hospitalized with congestive heart failure

Background: Congestive heart failure (CHF) is an increasingly prevalent poor-prognosis condition for which effective interventions are available. It is -therefore important to determine the extent to which patients with CHF receive appropriate care in Australian hospitals and identify ways for improving suboptimal care, if it exists. Aim: To evaluate the quality of in-hospital acute care of patients with CHF using explicit quality indicators based on published guidelines. Methods: A retrospective case note review was -performed, involving 216 patients admitted to three teaching hospitals in Brisbane, Queensland, Australia, between October 2000 and April 2001. Outcome measures were process-of-care quality -indicators calculated as proportions of all, or strongly -eligible (ideal), patients who received -specific interventions. Results: Assessment of underlying causes and acute precipitating factors was undertaken in 86% and 76% of patients, respectively, and objective evaluation of left ventricular function was performed in 62% of patients. Prophylaxis for deep venous thrombosis (DVT) was used in only 29% of ideal patients. Proportions of ideal patients receiving pharmacological treatments at discharge were: (i) angiotensin--converting enzyme inhibitors (ACEi) (82%), (ii) target doses of ACEi (61%), (iii) alternative vasodilators in patients ineligible for ACEi (20%), (iv) beta-blockers (40%) and (v) warfarin (46%). Conclusions: Opportunities exist for improving quality of in-hospital care of patients with CHF, -particularly for optimal prescribing of: (i) DVT prophylaxis, (ii) ACEi, (iii) second-line vasodilators, (iv) beta-blockers and (v) warfarin. More research is needed to identify methods for improving quality of in-hospital care.

Avaliação do perfil hemodinâmico de válvulas aórticas percutâneas: análise comparativa entre os dois dispositivos disponíveis no mercado - válvula auto-expansível e válvula expansível por balão

Mestrado em Tecnologia de Diagnóstico e Intervenção Cardiovascular. Área de especialização: Intervenção Cardiovascular.

Deformação miocárdica analisada por Speckle Tracking, em doentes hipertensos com fracção de ejecção preservada

Mestrado em Tecnologia de Diagnóstico e Intervenção Cardiovascular - Área de especialização: Ultrassonografia Cardiovascular.

Perfil ecocardiográfico do doente com estenose aórtica degenerativa

Mestrado em Tecnologia de Diagnóstico e Intervenção Cardiovascular - Área de especialização: Ultrassonografia Cardiovascular.

Avaliação da torção miocárdica, por Spekle Tracking, em doentes com HTA

Mestrado em Tecnologia de Diagnóstico e Intervenção Cardiovascular - Ramo de especialização: Ultrassonografia Cardiovascular

Cyclosporine versus tacrolimus: cost-effectiveness analysis for renal transplantation in Brazil

OBJECTIVE To analyze the cost-effectiveness of treatment regimens with cyclosporine or tacrolimus, five years after renal transplantation.METHODS This cost-effectiveness analysis was based on historical cohort data obtained between 2000 and 2004 and involved 2,022 patients treated with cyclosporine or tacrolimus, matched 1:1 for gender, age, and type and year of transplantation. Graft survival and the direct costs of medical care obtained from the National Health System (SUS) databases were used as outcome results.RESULTS Most of the patients were women, with a mean age of 36.6 years. The most frequent diagnosis of chronic renal failure was glomerulonephritis/nephritis (27.7%). In five years, the tacrolimus group had an average life expectancy gain of 3.96 years at an annual cost of R$78,360.57 compared with the cyclosporine group with a gain of 4.05 years and an annual cost of R$61,350.44.CONCLUSIONS After matching, the study indicated better survival of patients treated with regimens using tacrolimus. However, regimens containing cyclosporine were more cost-effective.

Dispersão da Refractariedade Auricular como Substrato Electrofisiológico da Vulnerabilidade Auricular em Doentes com Fibrilhação Auricular Paroxística

Atrial electrical remodeling plays a part in recurrence of atrial fibrillation (AF). It has been related to an increase in heterogeneity of atrial refractoriness that facilitates the occurrence of multiple reentry wavelets and vulnerability to AF. AIM: To examine the relationship between dispersion of atrial refractoriness (Disp_A) and vulnerability to AF induction (A_Vuln) in patients with clinical paroxysmal AF (PAF). METHODS: Thirty-six patients (22 male; age 55+/-13 years) with > or =1 year of history of PAF (no underlying structural heart disease--n=20, systemic hypertension--n=14, mitral valve prolapse--n=1, surgically corrected pulmonary stenosis--n=1), underwent electrophysiological study (EPS) while off medication. The atrial effective refractory period (AERP) was assessed at five different sites--high (HRA) and low (LRA) lateral right atrium, high interatrial septum (IAS), proximal (pCS) and distal (dCS) coronary sinus--during a cycle length of 600 ms. AERP was taken as the longest S1-S2 interval that failed to initiate a propagation response. Disp_A was calculated as the difference between the longest and shortest AERP. A_Vuln was defined as the ability to induce AF with 1-2 extrastimuli or with incremental atrial pacing (600-300 ms) from the HRA or dCS. The EPS included analysis of focal electrical activity based on the presence of supraventricular ectopic beats (spontaneous or with provocative maneuvers). The patients were divided into group A--AF inducible (n=25) and group B--AF not inducible (n=11). Disp_A was analyzed to determine any association with A_Vuln. Disp_A and A_Vuln were also examined in those patients with documented repetitive focal activity. Logistic regression was used to determine any association of the following variables with A_Vuln: age, systemic hypertension, left ventricular hypertrophy, left atrial size, left ventricular function, duration of PAF, documented atrial flutter/tachycardia and Disp_A. RESULTS: There were no significant differences between the groups with regard to clinical characteristics and echocardiographic data. AF was inducible in 71% of the patients and noninducible in 29%. Group A had greater Disp_A compared to group B (105+/-78 ms vs. 49+/-20 ms; p=0.01). Disp_A was >40 ms in 50% of the patients without A_Vuln and in 91% of those with A_Vuln (p=0.05). Focal activity was demonstrated in 14 cases (39%), 57% of them with A_Vuln. Disp_A was 56+/-23 ms in this group and 92+/-78 ms in the others (p=0.07). Using logistic regression, the only predictor of A_Vuln was Disp_A (p=0.05). CONCLUSION: In patients with paroxysmal AF, Disp_A is a major determinant of A_Vuln. Nevertheless, the degree of nonuniformity of AERP appears to be less important as an electrophysiological substrate for AF due to focal activation.

Origem Anómala da Artéria Coronária Esquerda a Partir da Artéria Pulmonar

OBJECTIVE: To assess the frequency and severity of the anomalous origin of the left coronary artery (ALCA) from the pulmonary artery (PA). DESIGN OF THE STUDY: Prospective study of case series between March 1991 and December 1994. SETTING: Referral-based Paediatric Cardiology Department of a Tertiary Care Center. PATIENTS AND METHODS: Five consecutive patients (pts) with anomalous origin of the LCA from the PA; there were three infants aged 4 months and two children one 8 year and one 9 year old. There were three girls and two boys. All pts had clinical and 2D-echo and Doppler investigation prior to cardiac catheterization (CC). Indication for CC was based in the association of symptoms and signs of myocarditis or dilated cardiomyopathy of acute or subacute onset and electrocardiographic (ECG) signs of ischemia in infants. In older patients (pts) diagnosis was suspected mainly from ECG. During CC in all pts, aortograms and when necessary selective coronary angiograms were performed. Surgical correction was performed in all children. In two pts stress exercise ECG and stress Thallium studies before and after surgery were performed. RESULTS: two pts had "adult" an three had "infantile" type of ALCA from the PA. CC was performed and diagnosis was confirmed at surgery in all cases. In one child, correct diagnosis was made by ECO prior to CC and in one case LCA to PA fistula was suspected on Colour-Doppler study. No complications were attributed to CC. Several types of surgery were performed: reimplantation of the ALCA from the PA to the aorta (three pts); tunnel connection of the aorta to the ALCA via the PA (one pt) and left internal mammary to LCA anastomosis (one pt). Two infants died intraoperatively due to extensive myocardial infarction and poor left ventricular function. All the three survivors are asymptomatic after a mean follow up of 34 months. Two oldest pts are currently in New York Heart Association functional class I with normal ECG and improved myocardial perfusion on Thallium scan despite almost total occlusion of LCA at the site of implantation in the aorta as diagnosed on coronary angiogram. CONCLUSIONS: ALCA from PA is associated with major morbidity and mortality. Diagnosis should be suspected in pts with unexplained myocardial ischemia on ECG and even more if it is associated to clinical signs of dilated cardiomyopathy or myocarditis. Careful assessment on ECO and pulsed Doppler and colour flow mapping should make the diagnosis in most cases. Although surgery can be performed based only on ECO diagnosis, we strongly advise for angiography in all cases as in our experience there are false negative diagnosis by ECO. Preoperative Thallium studies can be useful for the selection of the type of surgery as pts with very little viable myocardium will not survive the establishment of a direct systemic to coronary blood flow and may be candidates for heart transplantation.

Impacto da Idade no Tratamento e Resultados Após Enfarte Agudo do Miocárdio em Particular nos Muito Idosos

INTRODUCTION: The elderly population admitted for acute myocardial infarction is increasing. This group is not well studied in international trials and is probably treated with a more conservative approach. OBJECTIVES: To evaluate the presentation and treatment of myocardial infarction according to age, particularly in very elderly patients. METHODS: We studied 1242 consecutive patients admitted with acute myocardial infarction, assessing in-hospital, 30-day and one-year mortality during follow-up for each age-group. Patients were divided into four groups according to age: <45 years (7.6%); 45-64 years (43.3%); 65-74 years (23.4%); and ≥75 years (25.7%). RESULTS: Elderly patients had a worse risk profile (except for smoking), more previous history of coronary disease and a worse profile on admission, with the exception of lipid profile, which was more favorable. With regard to treatment of the elderly, although less optimized than in other age-groups, it was significantly better compared to other registries, including for percutaneous coronary angioplasty. Both complications and mortality were worse in the older groups. In elderly patients (≥75 years), adjusted risk of mortality was 4.9-6.3 times higher (p<0.001) than patients in the reference age-group (45-64 years). In these patients, the independent predictors of death were left ventricular function and renal function, use of beta-blockers being a predictor of survival. CONCLUSIONS: Elderly patients represent a substantial proportion of the population admitted with myocardial infarction, and receive less evidenced-based therapy. Age is an independent predictor of short- and medium-term mortality.

Stress-Related Mucosal Disease: Incidence of Bleeding and the Role of Omeprazole in its Prophylaxis

BACKGROUND: Upper gastrointestinal bleeding is the severe complication of stress-related mucosal disease in hospitalized patients. In intensive care units (ICU), risk factors are well defined and only mechanical ventilation and coagulopathy proved to be relevant for significant bleeding. On the contrary, in non-ICU settings there is no consensus about this issue. Nevertheless, omeprazole is still widely used in prophylaxis of bleeding. The objective of our study was to evaluate the relevance of stress-related mucosal disease bleeding in patients admitted to an internal medicine ward, and the role of omeprazole in its prophylaxis. METHODS: We conducted a retrospective study in which we analysed consecutive patients who were admitted to our ward over a year. We recorded demographic characteristics of the patients, potential risk factors for stress-related mucosal disease (clinical data, laboratory, and medication), administration of prophylactic omeprazole, and total cost of this prophylaxis. Patients with active gastrointestinal bleeding on the admission were excluded. We recorded every upper gastrointestinal bleeding event with clinical relevance. RESULTS: Five hundred and thirty-five patients, mean age 70 years, mean length of stay 9.6+/-7.7 days; 140 (26.2%) patients were treated with 40 mg of omeprazole intravenously, 193 (36.1%) with 20mg of omeprazole orally, and 202 (37.8%) patients had no prophylaxis. There was only one episode (0.2%) of clinically relevant bleeding. CONCLUSION: In patients admitted to an internal medicine ward, incidence of upper gastrointestinal bleeding as a complication of stress-related mucosal disease is low. We found that there is no advantage in prophylaxis with omeprazole.